title: Identification and structure-activity relationship study of carvacrol derivatives as Mycobacterium tuberculosis chorismate mutase inhibitors.
abstract: In the present study, we identified carvacrol, a major phenolic component of oregano oil as a novel small molecule inhibitor of Mycobacterium tuberculosis (MTB) chorismate mutase (CM) enzyme with IC50 of 1.06 ± 0.4 µM. Virtual screening of the BITS-Pilani in-house database using the crystal structure of the MTB CM bound transition state intermediate (PDB: 2FP2) as framework identified carvacrol as a potential lead. Further various carvacrol derivatives were evaluated in vitro for their ability to inhibit MTB CM enzyme, whole cell MTB and cytotoxicity as steps toward the derivation of structure-activity relationships (SAR) and lead optimization.
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad , Andhra Pradesh , India.
authors.forename: Reshma
authors.initials: R
authors.lastname: Alokam
authors.forename: Variam Ullas
authors.initials: VU
authors.lastname: Jeankumar
authors.forename: Jonnalagadda Padma
authors.initials: JP
authors.lastname: Sridevi
authors.forename: Siddharth Sai
authors.initials: SS
authors.lastname: Matikonda
authors.forename: Santosh
authors.initials: S
authors.lastname: Peddi
authors.forename: Mallika
authors.initials: M
authors.lastname: Alvala
authors.forename: Perumal
authors.initials: P
authors.lastname: Yogeeswari
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002826:Chorismate Mutase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000081007:Cymenes; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D039821:Monoterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009169:Mycobacterium tuberculosis / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000081007:Cymenes; D004791:Enzyme Inhibitors; D039821:Monoterpenes; C073316:carvacrol; D002826:Chorismate Mutase
keywords: Carvacrol; Mycobacterium tuberculosis; chorismate mutase